We retrospectively analyzed serum beta 2-microglobulin (beta 2M) levels in dialysis patients at our institution from 1986 through 1991 to determine the clinical significance of serum beta 2M levels in dialysis patients and to provide further insight into the pathogenesis of beta 2M-associated dialysis arthropathy. We analyzed the relationship between serum beta 2M values can the dialysis modality (hemodialysis and continuous ambulatory peritoneal dialysis [CAPD]), the duration of dialysis therapy, the type of hemodialyzer used, and the level of intrinsic glomerular filtration rate (GFR). The most important relationship observed in all dialysis patients was a significant inverse relationship between intrinsic GFR and serum beta 2M values. For all dialysis patients (hemodialysis and CAPD), serum beta 2M values were highest when the intrinsic GFR was less than 2.1 ml/min. There were no differences in serum beta 2M values between hemodialysis patients and CAPD patients or among patients using different types of cellulose-based hemodialyzers. As patients changed use from cellulose-based dialyzers to polysulfone dialyzers, there was no decline in serum beta 2M values. Exclusive treatment with polysulfone dialyzers for 9 to 12 months after initiation of long-term dialysis also led to no differences in serum beta 2M values compared with those in patients using cellulose-based dialyzers. At very low levels of intrinsic GFR (< 2.1 ml/min), hemodialysis patients using polysulfone dialyzers had lower levels of serum beta 2M than hemodialysis patients using cellulose-based dialyzers; CAPD patients also had lower levels of serum beta 2M than cellulose dialyzer-treated hemodialysis patients when the intrinsic GFR was less than 2.1 ml/min. All hemodialysis patients using cellulose dialyzers and CAPD patients were categorized at last follow-up as having definite, probable, or no evidence of beta 2M-associated dialysis arthropathy on the basis of clinical and radiographic criteria. We noted no significant differences in serum beta 2M values, regardless of the clinical diagnosis with regard to beta 2M-related amyloidosis. Patients with beta 2M amyloidosis had undergone dialysis therapy for a longer duration and had a larger cumulative exposure to beta 2M (the product of average serum beta 2M values and months of dialysis, or "beta 2M-months"). We conclude that the most important determinant of serum beta 2M values in dialysis patients is the remaining level of intrinsic GFR. At extremely low levels of GFR, use of polysulfone dialyzers or CAPD may lead to lower levels of serum beta 2M. Our analysis indicates that the duration of dialysis and cumulative exposure to beta 2M (beta 2M-months) are important factors in the development of clinically evident beta 2M amyloidosis.